Genetica has developed a novel retroviral technology (MaRX technology) for the genetic manipulation of both normal and tumor cells. It is the objective of the present proposal to enhance the scope and applicability of the MaRX technology. Specifically, MaRX will be developed as a tool not only for gain-of-function genetic screens but also most importantly loss-of-function genetic screens. This will be achieved in the present proposal by developing a warhead technology that when coupled with an antisense DNA construct, will render it capable of catalytically degrading a specific mRNA species. In the phase I application, the feasibility of this approach will be assessed with regard to the tumor suppressor genes p53, p16 and p21 as molecular models. The long term objective is to develop a technology that provides deeper insight into potential drug targets for oncogenic disease in man. PROPOSED COMMERCIAL APPLICATIONS: The technology development program proposed herein has a wide range of commercial applications, most specifically, the deployment of the technology for the discovery of novel drug targets. In addition, the technology has value per se to both the pharmaceutical and biotechnology industries.